A Novel Immunoregulatory PEGylated Poly(glycerol sebacate)/β-TCP Membrane for Application in Guided Bone Regeneration

The recently developed poly(ethylene glycol)ylated poly(glycerol sebacate)/β-tricalcium phosphate (PEGS/β-TCP) membrane possesses favorable mechanical properties and excellent osteogenic activity. This study is designed to evaluate the feasibility of applying PEGS/β-TCP membrane in guided bone regeneration (GBR) through investigating the in vitro and in vivo activities of macrophages promoted by PEGS/β-TCP membranes during osteogenesis. The behavior of macrophages seeded on PEGS/β-TCP and PEGS membranes is assessed in terms of cell viability, polarization pattern, and release of inflammatory and osteogenic cytokines. The in vitro osteogenic effect of PEGS/β-TCP membrane-associated macrophage polarization is evaluated by incubating mesenchymal stem cells (MSCs) with conditioned medium derived from macrophages stimulated with PEGS/β-TCP or PEGS membranes. The in vivo correlation between macrophage polarization and PEGS/β-TCP membrane-driven osteogenesis is investigated using a rat calvarial defect model. The results show that PEGS/β-TCP and PEGS membranes are capable of downregulating M1 polarization and upregulating M2 polarization. Compared to the PEGS membrane, the PEGS/β-TCP membrane can further alleviate local inflammatory response and significantly promote the in vitro osteogenic differentiation of MSCs and in vivo restoration of bone defects. In conclusion, the novel PEGS/β-TCP membrane can promote the osteogenic commitment of MSCs and restore calvarial bone defects by improving the macrophage polarization pattern.